1. Technical Field
The invention relates to methods for solid phase chemical synthesis. Specifically, the invention provides efficient methods for loading amino derivatives onto trityl chloride resins, and for cleaving modified amino derivatives from a resin. The invention also provides novel chemically modified amino derivatives made by these methods.
2. Background Information
Combinatorial chemistry and automated organic synthesis have been used to generate collections of molecules, or “libraries.” As the size of such a library grows, so does the likelihood that it will contain individual molecules having activities suitable for treating human, animal, or plant diseases. Solid-supported methodologies have proven useful to create large chemical libraries.
Trityl chloride resins have been used to immobilize alcohols and amines, typically for solid-supported synthesis of peptides (See e.g., Leznoff, Acc. Chem. Res. 1978 11, 327; Chen et al., J. Am. Chem. Soc. 1994, 116, 2661; Bunin, The Combinatorial Index, Academic Press, San Diego, 1998; Barlos et al., Liebigs Ann. Chem. 1988, 1079; Barlos, et al. Tetrahedron Lett. 1989 30, 3943). A generalized solid phase synthesis scheme utilizing trityl chloride resins is depicted in FIG. 1. One advantage of using trityl chloride resins over other resins is that trityl chloride resins can be regenerated (e.g., by treating the hydroxytrityl resins that remain after cleaving product from the resin with SOCl2).